Dynamic metabotropic control of intrinsic firing in cerebellar unipolar brush cells.
Neuronal firing is regulated by the complex interaction of multiple depolarizing and hyperpolarizing currents; intrinsic firing, which defines the neuronal ability to generate action potentials in the absence of synaptic excitation, is particularly sensitive to modulation by currents that are active below the action potential threshold. Cerebellar unipolar brush cells (UBCs) are excitatory granule layer interneurons that are capable of intrinsic firing; here we show that, in acute mouse cerebellar slices, barium-sensitive background potassium channels of UBCs effectively regulate intrinsic firing. We also demonstrate that these channels are regulated by group II metabotropic glutamate receptors (mGluRs), which we show to be present in both of the known subsets of UBCs, one of which expresses calretinin and the other mGluR1alpha. Finally, we show that background potassium currents controlling UBCs' firing are mediated by at least two channel types, one of which is sensitive and the other insensitive to the GIRK blocker tertiapin. Thus in UBCs, glutamatergic transmission appears to have a complex bimodal effect: although it increases spontaneous firing through activation of ionotropic receptors, it also has inhibitory effects through the mGluR-dependent activation of tertiapin-sensitive and -insensitive background potassium currents.
Russo
Marco J
MJ
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Yau
Hau-Jie
HJ
Nunzi
Maria-Grazia
MG
Mugnaini
Enrico
E
Martina
Marco
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001514:Bee Venoms / Q000494:pharmacology; D064032:Calbindin 2; D002531:Cerebellum / Q000166:cytology*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D001514:Bee Venoms; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D026902:Potassium Channel Blockers; D018094:Receptors, Metabotropic Glutamate; D064030:S100 Calcium Binding Protein G; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C104077:metabotropic glutamate receptor type 1; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D001464:Barium; C029738:tertiapin